类生物合成酶通过两种不同的机制产生二聚合物对
Shinji Kishimoto1, Yuya Matsubara1, Kenji Watanabe1
1Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Journal of the American Chemical Society
|March 18, 2022
概括
研究人员从阿斯伯吉勒斯 (Aspergillus lentulus) 发现了一种新型的类似埃尔戈培的化合物, 这些化合物具有独特的肉酸部分和不典型的生物合成途径,涉及二基托皮帕津的形成和立体特异反应.
科学领域:
- 自然产品化学
- 菌群学
- 生物化学
背景情况:
- 厄尔戈是一种具有三延伸的厄尔戈类.
- 纤维状真菌,如阿斯伯吉勒斯物种,是众所周知的各种自然产品的来源.
- 了解真菌的二次代谢对于发现新生物活性化合物至关重要.
研究的目的:
- 发现并从结构上描述来自*Aspergillus lentulus*的新型类化合物.
- 阐明这些新型化合物的非典型生物合成途径,
- 调查负责培形成的酶机制.
主要方法:
- 隔离和结构特征的lentopeptins.
- 基因组测序和基因群的识别.
- 针对基因删除以研究生物合成途径.
- 在体外鉴定非核糖体合成酶 (LenA) 和P450酶 (LenC).
- 特定地点的突变性研究.
主要成果:
- 发现了伦托佩,一种类似于埃尔戈佩的化合物,其中含有肉酸,而不是酸.
- 鉴定了一种不典型的生物合成途径,涉及基素的释放.
- 通过LenC释独特的酶机制,通过立体特异的化/脱和水化产生两种异构体产物 (lentopeptin A和B).
- 对化-终端凝结类 (T-CT) 滴域和P450酶的新型催化活性的证明.
结论:
- 大自然以新的方式利用常见的生物合成酶来制造复杂的天然产品.
- 伦托佩的发现扩大了已知的埃尔戈佩类化合物的结构多样性.
- 已确定的生物合成途径为真菌的二次代谢和酶进化提供了洞察力.
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